Did Researchers Just Discover a Functional Cure for Duchenne Muscular Dystrophy?

Muscular dystrophy is a frightening and progressive disease that's derived from an inherited gene mutation that leads to the wasting away of an affected person's muscles, resulting in eventual loss of muscle function, and in some cases, even leading to death.

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While there are multiple types of muscular dystrophy, Duchenne muscular dystrophy, also known as DMD, is arguably the most dangerous. In DMD patients, muscle fiber membranes designed to protect muscle fiber are damaged, allowing the protein responsible for muscle contraction to escape, and for the muscles to absorb excess calcium. Both factors work toward damaging and eventually killing off muscle fibers, resulting in progressive muscle degeneration.

According to the National Institutes of Health, somewhere between 1 in 3,500 and 1 in 6,000 male births each year are diagnosed with DMD in the United States. With the average diagnosis often coming between ages three and seven, most DMD patients won't live past their mid-20s. It's this dire timeline that has researchers scrambling for ways to treat DMD.

Exciting new research published this past week in EMBO Molecular Medicine suggests there could be a functional cure for DMD sooner than we imagined.

Source: BioMarin Pharmaceutical.

Could this be a cure for Duchenne muscular dystrophy?According to an 18-author international study, researchers were able to successfully grow muscle cells within a petri dish and subsequently graft those muscle cells into mice, where they became a normally contracting skeletal muscle.

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Researchers used mesoangioblasts, or muscle stem cells, grown in the presence of a supportive hydrogel, and modified these cells in such a way that nerve and blood vessel growth was stimulated. This was critical, because previous attempts to introduce externally grown muscle cells into a host body had proven unsuccessful, as the host didn't grow blood vessels or nerves for the transplanted muscle cells. In this study, following transplantation onto the surface of other muscle fibers underneath the skin of the trial mice, mature muscle fibers developed, forming a "complete and functional muscle within weeks."

The practical application of this technology would be to take a DMD patient's muscle cells, grow them in a supportive hydrogel, and reintroduce those cells in an area adjacent to damaged muscle. In theory, this implant could replace the damaged muscle in a fairly short span of time.

But, researchers also cautioned that this successful study by no means validates that the muscle-building process can be scaled to address human-related muscular dystrophy (at least yet). The next step for researchers is to test the muscle-regenerating model in larger animals before even attempting a human clinical trial.

Improvements could be around the cornerWhile a fully functional cure for DMD could still be years away, as researchers work out whether or not scaling its lab model will work in larger animals and eventually humans, there are DMD-specific treatments that could make an impact very soon.

Within the biotechnology sector, perhaps no company is the face of DMD research more so than Sarepta Therapeutics .

Source: Sarepta Therapeutics.

Sarepta Therapeutics' lead drug is eteplirsen, an RNA-interference drug designed to skip exon-51. There are many different types of DMD, and exon-51 is the most common, representing 13% of all DMD cases. Sarepta estimates that exon-skipping could treat 80% of all DMD cases and has seven additional exon-skipping drugs in its pipeline currently in the preclinical or discovery phase. These eight drugs (inclusive of eteplirsen) would cover nearly half of all DMD cases in the U.S. (and eventually worldwide were Sarepta to apply for approval in the EU and elsewhere).

Prior to eteplirsen, which is designed to stimulate the production of dystrophin and ultimately keep muscle fiber membranes intact, no drug had slowed the progression of DMD. But, in Sarepta's phase 2 48-week update, the results for the intent-to-treat group actually showed an improvement in the six-minute walk test, or 6MWT, from baseline. This was unheard of, and it put eteplirsen on the radar.

Since this update, things have normalized a bit, with the 168-week update showing a 76.7-meter reduction in the 6MWT from baseline. While some people would be disappointed by the drop-off in the 6MWT (which has been accelerating over the past 48 weeks), it still represents a statistically significant 65.4-meter benefit over the control group that was switched to eteplirsen (and who saw their 6MWT figures stabilize) at a later date.

Source: Sarepta Therapeutics.

Sarepta began enrolling for a confirmatory phase 3 study of eteplirsen late last year and plans to submit a new drug application with the Food and Drug Administration by mid-year.

The other player in this space is BioMarin Pharmaceutical , which purchased clinical-stage biopharmaceutical company Prosensa for up to $840 million, depending on near-term milestones. Prosensa's lead experimental DMD drug, drisapersen, failed to meet its primary endpoint in a broad phase 3 study despite producing encouraging phase 2 results. However, after diving deeper into the data, Prosensa announced its belief that drisapersen could be a useful agent in earlier stages of DMD, and as such, it's being explored in those earlier indications. It still remains to be seen whether BioMarin is going to get its money's worth from the Prosensa purchase, but DMD patients and their parents are clearly holding out hope for an improvement in their quality of life.

A reality checkAlthough Sarepta's phase 2b extension study has been encouraging, DMD patients and investors should also take two additional factors into consideration.

First, there have been a number of miscommunications between Sarepta and the FDA that have delayed a new drug filing for eteplirsen. Consider it a possibility that the FDA will want to see a full 48 weeks of data in Sarepta's phase 3 study before considering an approval. This would put a possible approval off until mid-2016, or even 2017.

The other factor worth mentioning here is that eteplirsen's approval isn't a lock. Despite the utter lack of other medicines designed to treat DMD, the FDA has expressed concern about using increased dystrophin production as a primary endpoint. Because Sarepta's DMD pipeline revolves entirely around the exon-skipping model, a failure of eteplirsen to be approved, or for the FDA to validate its exon-skipping pathway, could be disastrous for the company.

One thing for certain is that time is of the essence with DMD patients, and we desperately need therapies designed to slow or stop the progression of the disease. Eteplirsen very well could be the solution for the next few years -- or even longer -- until a function cure for DMD is actually a reality. I look forward to ongoing innovation in this space and hope that serious strides can be made to improve DMD patients' quality of life and survival.